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Losartan Alleviates the Side Effects and Maintains the Anticancer Activity of Axitinib

Ying Fu1, Rengui Saxu1, Kadir Ahmad Ridwan1

  • 1China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, College of Bioengineering, Tianjin University of Science and Technology, Tianjin 300457, China.

Molecules (Basel, Switzerland)
|May 14, 2022
PubMed

Insights

Losartan effectively mitigates severe side effects of axitinib, a potent vascular endothelial growth factor (VEGF) receptor inhibitor, without compromising its antitumor efficacy. This combination therapy improves patient outcomes by managing hypertension and reducing adverse events.

Area of Science:

  • Oncology
  • Pharmacology
  • Cardiovascular Medicine

Background:

  • Axitinib, a potent vascular endothelial growth factor (VEGF) receptor inhibitor, exhibits significant antitumor activity but causes severe side effects.
  • Losartan, an angiotensin receptor blocker, manages hypertension and associated complications.
  • The clinical utility of axitinib is limited by its adverse effects, necessitating strategies to improve patient tolerability.

Purpose of the Study:

  • To investigate the potential of losartan in ameliorating axitinib-induced side effects.
  • To evaluate the impact of losartan on the antitumor activity of axitinib.
  • To determine the combined effects of axitinib and losartan in preclinical models.

Main Methods:

  • Wistar rat model to assess blood pressure changes and side effect amelioration.
  • Miles experimental model to evaluate vascular permeability.
  • Mouse xenograft tumor model to assess antitumor efficacy.

Main Results:

  • Axitinib treatment significantly increased systolic blood pressure in Wistar rats.
  • Co-administration of losartan markedly reduced the blood pressure elevation induced by axitinib.
  • Losartan did not significantly affect axitinib's low vascular permeability or its antitumor activity in preclinical models.

Conclusions:

  • Combination therapy with axitinib and losartan effectively reduces axitinib-related side effects, primarily hypertension.
  • Losartan preserves the antitumor efficacy of axitinib, suggesting a favorable therapeutic window.
  • This study offers a potential strategy to overcome the tolerability issues associated with VEGF receptor inhibitors.
Keywords:
VEGF receptor inhibitorangiotensin receptor blockersantitumoraxitiniblosartanside effect

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